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PAVEL GERSHKOVICH's Outputs (54)

Rapeseed oleosomes facilitate intestinal lymphatic delivery and oral bioavailability of cannabidiol (2024)
Journal Article
Ji, L., Feng, W., Chen, H., Chu, Y., Wong, A., Zhu, Y., Sinatra, G., Bramante, F., Carrière, F., Stocks, M. J., di Bari, V., Gray, D. A., & Gershkovich, P. (2024). Rapeseed oleosomes facilitate intestinal lymphatic delivery and oral bioavailability of cannabidiol. International Journal of Pharmaceutics, Article 124947. https://doi.org/10.1016/j.ijpharm.2024.124947

Due to high lipophilicity and extensive first-pass metabolic loss, cannabidiol (CBD) has low oral bioavailability. Co-administration of CBD and long-chain lipids facilitates the intestinal lymphatic delivery, resulting in higher systemic bioavailabil... Read More about Rapeseed oleosomes facilitate intestinal lymphatic delivery and oral bioavailability of cannabidiol.

Delivery of imiquimod to intestinal lymph nodes following oral administration (2024)
Journal Article
Chen, H., Ji, L., Wong, A., Chu, Y., Feng, W., Zhu, Y., Wang, J., Comeo, E., Kim, D.-H., Stocks, M. J., & Gershkovich, P. (2024). Delivery of imiquimod to intestinal lymph nodes following oral administration. International Journal of Pharmaceutics, 667, Article 124895. https://doi.org/10.1016/j.ijpharm.2024.124895

Intestinal lymph nodes are involved in the progression of colorectal cancer (CRC). Tumours suppress the activation of dendritic cells (DCs) in draining lymph nodes, diminishing anti-cancer immune response. Imiquimod (IMQ) facilitates DCs activation v... Read More about Delivery of imiquimod to intestinal lymph nodes following oral administration.

Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents (2024)
Journal Article
Brookes, A., Kindon, N., Scurr, D., Alexander, M., Gershkovich, P., & BRADSHAW, T. (2024). Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents. British Journal of Cancer, 2, Article 67. https://doi.org/10.1038/s44276-024-00088-0

Background
Glioblastoma multiforme (GBM) is an aggressive cancer with poor prognosis, partly due to resistance to the standard chemotherapy treatment, temozolomide (TMZ). Phytocannabinoid cannabidiol (CBD) has exhibited anti-cancer effects against G... Read More about Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents.

Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents (2024)
Journal Article
Brookes, A., Kindon, N., Scurr, D. J., Alexander, M. R., Gershkovich, P., & Bradshaw, T. (2024). Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents. BJC Reports, 2, Article 67. https://doi.org/10.1038/s44276-024-00088-0

Background
Glioblastoma multiforme (GBM) is an aggressive cancer with poor prognosis, partly due to resistance to the standard chemotherapy treatment, temozolomide (TMZ). Phytocannabinoid cannabidiol (CBD) has exhibited anti-cancer effects against G... Read More about Cannabidiol and fluorinated derivative anti-cancer properties against glioblastoma multiforme cell lines, and synergy with imidazotetrazine agents.

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review (2024)
Journal Article
Akbar, T., Gershkovich, P., Stamatopoulos, K., Gowland, P. A., Stolnik, S., Butler, J., & Marciani, L. (2024). Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review. Molecular Pharmaceutics, 21(4), 1553-1562. https://doi.org/10.1021/acs.molpharmaceut.3c01123

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial... Read More about Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport (2023)
Journal Article
Chu, Y., Wong, A., Chen, H., Ji, L., Qin, C., Feng, W., …Gershkovich, P. (2023). Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport. European Journal of Pharmaceutics and Biopharmaceutics, 191, 90-102. https://doi.org/10.1016/j.ejpb.2023.08.015

The establishment of latent cellular and anatomical viral reservoirs is a major obstacle to achieving a cure for people infected by HIV. Mesenteric lymph nodes (MLNs) are one of the most important anatomical reservoirs of HIV. Suboptimal levels of an... Read More about Development of lipophilic ester prodrugs of dolutegravir for intestinal lymphatic transport.

Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain (2023)
Journal Article
Muresan, P., Woodhams, S., Smith, F., Taresco, V., Shah, J., Wong, M., …Marlow, M. (2023). Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain. Nanomedicine: Nanotechnology, Biology and Medicine, 49, Article 102664. https://doi.org/10.1016/j.nano.2023.102664

We investigated how the biodistribution of cannabidiol (CBD) within the central nervous system (CNS) is influenced by two different formulations, an oil-in-water (O/W) nanoemulsion and polymer-coated nanoparticles (PCNPs). We observed that both CBD f... Read More about Evaluation of cannabidiol nanoparticles and nanoemulsion biodistribution in the central nervous system after intrathecal administration for the treatment of pain.

Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain (2023)
Journal Article
Brookes, A., Jewell, A., Feng, W., Bradshaw, T. D., Butler, J., & Gershkovich, P. (2023). Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain. International Journal of Pharmaceutics, 635, Article 122651. https://doi.org/10.1016/j.ijpharm.2023.122651

Delivery to the brain is a challenging task due to its protection by the blood–brain barrier (BBB). Lipids and fatty acids are reported to affect the permeability of the BBB, although this has not been reported following oral administration. Cannabid... Read More about Oral lipid-based formulations alter delivery of cannabidiol to different anatomical regions in the brain.

Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site (2022)
Journal Article
Muresan, P., McCrorie, P., Smith, F., Vasey, C., Taresco, V., Scurr, D. J., …Marlow, M. (2023). Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site. European Journal of Pharmaceutics and Biopharmaceutics, 182, 53-61. https://doi.org/10.1016/j.ejpb.2022.11.016

Systemic drug delivery to the central nervous system (CNS) has been historically impeded by the presence of the blood brain barrier rendering many therapies inefficacious to any cancer cells residing within the brain. Therefore, local drug delivery s... Read More about Development of nanoparticle loaded microneedles for drug delivery to a brain tumour resection site.

Editorial: Lymphatic delivery and targeting of drugs, vaccines, and imaging agents (2022)
Journal Article
Han, S., Trevaskis, N., Gershkovich, P., & Kagan, L. (2022). Editorial: Lymphatic delivery and targeting of drugs, vaccines, and imaging agents. Frontiers in Pharmacology, 13, Article 1011778. https://doi.org/10.3389/fphar.2022.1011778

The lymphatic system plays a key role in the (patho) physiology of a number of diseases, including autoimmune/inflammatory disorders, cancer, infections, and metabolic syndrome. Biological pathways in the lymphatic system provide new promising treatm... Read More about Editorial: Lymphatic delivery and targeting of drugs, vaccines, and imaging agents.

Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol (2022)
Journal Article
Feng, W., Qin, C., Abdelrazig, S., Bai, Z., Raji, M., Darwish, R., …Gershkovich, P. (2022). Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol. International Journal of Pharmaceutics, 624, Article 121947. https://doi.org/10.1016/j.ijpharm.2022.121947

Although natural sesame oil has been shown to facilitate the lymphatic delivery and oral bioavailability of the highly lipophilic drug cannabidiol (CBD), considerable variability remains an unresolved challenge. Vegetable oils differ substantially in... Read More about Vegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol.

Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle (2022)
Journal Article
Jewell, A., Brookes, A., Feng, W., Ashford, M., Gellert, P., Butler, J., …Gershkovich, P. (2022). Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle. European Journal of Pharmaceutics and Biopharmaceutics, 174, 29-34. https://doi.org/10.1016/j.ejpb.2022.03.014

Efficient delivery of highly lipophilic drugs or prodrugs to the mesenteric lymph nodes (MLN) can be achieved following oral administration with lipids. However, it remains unclear which specific MLN can be targeted and to what extent. Moreover, the... Read More about Distribution of a highly lipophilic drug cannabidiol into different lymph nodes following oral administration in lipidic vehicle.

Is oral lipid-based delivery for drug targeting to the brain feasible? (2022)
Journal Article
Brookes, A., Ji, L., Bradshaw, T. D., Stocks, M., Gray, D., Butler, J., & Gershkovich, P. (2022). Is oral lipid-based delivery for drug targeting to the brain feasible?. European Journal of Pharmaceutics and Biopharmaceutics, 172, 112-122. https://doi.org/10.1016/j.ejpb.2022.02.004

This review outlines the feasibility of oral lipid-based targeted delivery of drugs to the brain, including permeation of the central nervous system's (CNS) protective blood–brain barrier (BBB). The structure of the BBB and disruption caused by varyi... Read More about Is oral lipid-based delivery for drug targeting to the brain feasible?.

Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers (2022)
Journal Article
Sulaiman, S., Gershkovich, P., Hoad, C. L., Calladine, M., Spiller, R. C., Stolnik, S., & Marciani, L. (2022). Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers. Pharmaceutics, 14(2), Article 270. https://doi.org/10.3390/pharmaceutics14020270

Oral specially coated formulations have the potential to improve treatment outcomes of a range of diseases in distal intestinal tract whilst limiting systemic drug absorption and adverse effects. Their development is challenging, partly because of li... Read More about Application of In Vivo MRI Imaging to Track a Coated Capsule and Its Disintegration in the Gastrointestinal Tract in Human Volunteers.

Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin (2021)
Journal Article
Al-Beltagi, S., Goulding, L. V., Chang, D. K., Mellits, K. H., Hayes, C. J., Gershkovich, P., …Chang, K.-C. (2021). Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin. Virulence, 12(1), 2946-2956. https://doi.org/10.1080/21505594.2021.2006960

The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for thei... Read More about Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin.

Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients (2021)
Journal Article
Jewell, A., Williams, H., Hoad, C. L., Gellert, P. R., Ashford, M. B., Butler, J., …Gershkovich, P. (2021). Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients. Pharmaceutics, 13(9), Article 1343. https://doi.org/10.3390/pharmaceutics13091343

Dietary lipids and some pharmaceutical lipid excipients can facilitate the targeted delivery of drugs to the intestinal lymphatics. Here, the feasibility of magnetic resonance imaging (MRI) for imaging lipid uptake into the intestinal lymphatics was... Read More about Assessing lymphatic uptake of lipids using magnetic resonance imaging: A feasibility study in healthy human volunteers with potential application for tracking lymph node delivery of drugs and formulation excipients.

Chemosensitization of temozolomide-resistant pediatric diffuse midline glioma using potent nanoencapsulated forms of a N(3)-propargyl analogue (2021)
Journal Article
Heravi Shargh, V., Luckett, J., Bouzinab, K., Paisey, S., Turyanska, L., Singleton, W. G., …Coyle, B. (2021). Chemosensitization of temozolomide-resistant pediatric diffuse midline glioma using potent nanoencapsulated forms of a N(3)-propargyl analogue. ACS Applied Materials and Interfaces, 13(30), 35266-35280. https://doi.org/10.1021/acsami.1c04164

The lack of clinical response to the alkylating agent temozolomide (TMZ) in pediatric diffuse midline/intrinsic pontine glioma (DIPG) has been associated with O6-methylguanine-DNA-methyltransferase (MGMT) expression and mismatch repair deficiency. He... Read More about Chemosensitization of temozolomide-resistant pediatric diffuse midline glioma using potent nanoencapsulated forms of a N(3)-propargyl analogue.

Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes (2021)
Journal Article
Sheriston, C., Medrano-Padial, C., Qin, C., Fischer, P. M., Feng, W., Chu, Y., …Ling, B. (2021). Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes. International Journal of Pharmaceutics, 602, Article 120621. https://doi.org/10.1016/j.ijpharm.2021.120621

The introduction of combination antiretroviral therapy (cART) led to substantial improvement in mortality and morbidity of HIV-1 infection. However, the poor penetration of antiretroviral agents to HIV-1 reservoirs limit the ability of the antiretrov... Read More about Oral administration of tipranavir with long-chain triglyceride results in moderate intestinal lymph targeting but no efficient delivery to HIV-1 reservoir in mesenteric lymph nodes.

Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol (2021)
Journal Article
Feng, W., Qin, C., Chu, Y. J., Berton, M., Lee, J. B., Zgair, A., …Gershkovich, P. (2021). Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol. European Journal of Pharmaceutics and Biopharmaceutics, 162, 43-49. https://doi.org/10.1016/j.ejpb.2021.02.013

© 2021 Elsevier B.V. Lipid-based formulations play a significant role in oral delivery of lipophilic drugs. Previous studies have shown that natural sesame oil promotes the intestinal lymphatic transport and oral bioavailability of the highly lipophi... Read More about Natural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol.

Structure-based design of highly selective 2,4,5-trisubstituted pyrimidine CDK9 inhibitors as anti-cancer agents (2021)
Journal Article
Shao, H., Foley, D. W., Huang, S., Abbas, A. Y., Lam, F., Gershkovich, P., …Wang, S. (2021). Structure-based design of highly selective 2,4,5-trisubstituted pyrimidine CDK9 inhibitors as anti-cancer agents. European Journal of Medicinal Chemistry, 214, Article 113244. https://doi.org/10.1016/j.ejmech.2021.113244

Cyclin-dependent kinases (CDKs) are a family of Ser/Thr kinases involved in cell cycle and transcriptional regulation. CDK9 regulates transcriptional elongation and this unique property has made it a potential target for several diseases. Due to the... Read More about Structure-based design of highly selective 2,4,5-trisubstituted pyrimidine CDK9 inhibitors as anti-cancer agents.

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus (2021)
Journal Article
Al-Beltagi, S., Preda, C. A., Goulding, L. V., James, J., Pu, J., Skinner, P., …Chang, K.-C. (2021). Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus. Viruses, 13(2), Article 234. https://doi.org/10.3390/v13020234

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to in-clude antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass va... Read More about Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus.

Strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate (2021)
Journal Article
Zgair, A., Dawood, Y., Ibrahem, S. M., Lee, J. B., Feng, W., Fischer, P. M., & Gershkovich, P. (2021). Strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate. Molecules, 26(1), Article 233. https://doi.org/10.3390/molecules26010233

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated met... Read More about Strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate.

Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach (2020)
Journal Article
Qin, C., Chu, Y., Feng, W., Fromont, C., He, S., Ali, J., …Gershkovich, P. (2021). Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach. Journal of Controlled Release, 329, 1077-1089. https://doi.org/10.1016/j.jconrel.2020.10.036

© 2020 Elsevier B.V. The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, inc... Read More about Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach.

Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone 3 undecanoate 4 (2020)
Journal Article
Zgair, A., Dawood, Y., Ibrahim, S. M., Back, H.-M., Kagan, L., Gershkovich, P., & Lee, J. B. (2020). Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone 3 undecanoate 4. Applied Sciences, 10(20), Article 7283. https://doi.org/10.3390/app10207283

The bioavailability of orally administered drugs could be impacted by intestinal and 12 hepatic first-pass metabolism. Testosterone undecanoate (TU), an orally administered ester prodrug 13 of testosterone, is significantly subjected to first-pass me... Read More about Predicting intestinal and hepatic first-pass metabolism of orally administered testosterone 3 undecanoate 4.

The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations (2020)
Journal Article
Franco, V., Gershkovich, P., Perucca, E., & Bialer, M. (2020). The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations. Clinical Pharmacokinetics, 59(12), 1493-1500. https://doi.org/10.1007/s40262-020-00931-w

For highly lipophilic drugs, passage into the intestinal lymphatic system rather than the portal vein following oral administration may represent a major alternative route of delivery into the general circulation. Increasing intestinal lymphatic tran... Read More about The Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations.

Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma (2020)
Journal Article
Qin, C., Feng, W., Chu, Y. J., Lee, J. B., Berton, M., Bettonte, S., …Gershkovich, P. (2020). Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma. Biomedical Chromatography, 34(11), Article e4934. https://doi.org/10.1002/bmc.4934

© 2020 The Authors. Biomedical Chromatography published by John Wiley & Sons Ltd A simple, sensitive and cost-effective HPLC-UV bioanalytical method for determination of lopinavir (LPV) in rat and human plasma was developed and validated. The plasm... Read More about Development and validation of a cost-effective and sensitive bioanalytical HPLC-UV method for determination of lopinavir in rat and human plasma.

Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer (2020)
Journal Article
Monteiro, P. F., Gulfam, M., Monteiro, C. J., Travanut, A., Abelha, T. F., Pearce, A. K., …Alexander, C. (2020). Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer. Journal of Controlled Release, 323, 549-564. https://doi.org/10.1016/j.jconrel.2020.04.049

© 2020 Elsevier B.V. Triple negative or basal-like breast cancer (TNBC) is characterised by aggressive progression, lack of standard therapies and poorer overall survival rates for patients. The bad prognosis, high rate of relapse and resistance agai... Read More about Synthesis of micellar-like terpolymer nanoparticles with reductively-cleavable cross-links and evaluation of efficacy in 2D and 3D models of triple negative breast cancer.

Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage (2020)
Journal Article
Bouzinab, K., Summers, H., Stevens, M. F., Moody, C. J., Thomas, N. R., Gershkovich, P., …Turyanska, L. (2020). Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage. ACS Applied Materials and Interfaces, 12(11), 12609-12617. https://doi.org/10.1021/acsami.0c01514

Glioblastoma multiforme (GBM) is a grade IV astrocytoma, which is the most aggressive form of brain tumor. The standard of care for this disease includes surgery, radiotherapy and temozolomide (TMZ) chemotherapy. Poor accumulation of TMZ at the tumor... Read More about Delivery of temozolomide and N3-propargyl analog to brain tumors using an apoferritin nanocage.

Is rat a good model for assessment of particulate-based taste-masked formulations? (2019)
Journal Article
Ali, J., Chiang, M., Lee, J. B., Voronin, G. O., Bennett, J., Cram, A., …Gershkovich, P. (2020). Is rat a good model for assessment of particulate-based taste-masked formulations?. European Journal of Pharmaceutics and Biopharmaceutics, 146, 1-9. https://doi.org/10.1016/j.ejpb.2019.11.001

Recently there has been an increased interest to develop specialised dosage forms that are better suited to specific patient populations, such as paediatrics and geriatrics. In these patient populations the acceptability of the oral dosage form can b... Read More about Is rat a good model for assessment of particulate-based taste-masked formulations?.

A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin (2019)
Journal Article
Lee, J. B., Radhi, M., Cipolla, E., Gandhi, R. D., Sarmad, S., Zgair, A., …Gershkovich, P. (2019). A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin. Scientific Reports, 9, Article 15760. https://doi.org/10.1038/s41598-019-52254-x

Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have st... Read More about A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin.

Solid lipid nanoparticles self-assembled from spray dried microparticles (2019)
Journal Article
Sanchez-Vazquez, B., Lee, J. B., Strimaite, M., Buanz, A., Bailey, R., Gershkovich, P., …Williams, G. R. (2019). Solid lipid nanoparticles self-assembled from spray dried microparticles. International Journal of Pharmaceutics, 572, Article 118784. https://doi.org/10.1016/j.ijpharm.2019.118784

We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When th... Read More about Solid lipid nanoparticles self-assembled from spray dried microparticles.

In search of effective therapies to overcome resistance to Temozolomide in brain tumours (2019)
Journal Article
Grundy, R., Bouzinab, K., Summers, H., Zhang, J., Stevens, M. F. G., Moody, C. J., …Bradshaw, T. D. (2019). In search of effective therapies to overcome resistance to Temozolomide in brain tumours. Cancer Drug Resistance, 2(4), 1018-1031. https://doi.org/10.20517/cdr.2019.64

Glioblastoma multiforme is the most common and lethal brain tumour-type. The current standard of care includes Temozolomide (TMZ) chemotherapy. However, inherent and acquired resistance to TMZ thwart successful treatment. The direct repair protein me... Read More about In search of effective therapies to overcome resistance to Temozolomide in brain tumours.

Codrug Approach for the Potential Treatment of EML4-ALK Positive Lung Cancer (2019)
Journal Article
Garces, A. E., Al-Hayali, M., Lee, J. B., Li, J., Gershkovich, P., Bradshaw, T. D., & Stocks, M. J. (2020). Codrug Approach for the Potential Treatment of EML4-ALK Positive Lung Cancer. ACS Medicinal Chemistry Letters, 11(3), 316-321. https://doi.org/10.1021/acsmedchemlett.9b00378

We report on the synergistic effect of PI3K inhibition with ALK inhibition for the possible treatment of EML4-ALK positive lung cancer. We have brought together ceritinib (ALK inhibitor) and pictilisib (PI3K inhibitor) into a single bivalent molecule... Read More about Codrug Approach for the Potential Treatment of EML4-ALK Positive Lung Cancer.

Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition (2019)
Journal Article
Hossan, M. S., Chan, Z. Y., Collins, H. M., Shipton, F. N., Butler, M. S., Rahmatullah, M., …Bradshaw, T. D. (2019). Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition. Cancer Letters, 453, 57-73. https://doi.org/10.1016/j.canlet.2019.03.034

Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin. Cerberin (CR), a cardenolide isolated from the fruit kernel of Cerbera odollam, was found to potently inhibit cancer cel... Read More about Cardiac glycoside cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition.

Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine (2018)
Journal Article
Ali, J., Zgair, A., Hameed, G. S., Garnett, M. C., Roberts, C. J., Burley, J. C., & Gershkovich, P. (2019). Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine. International Journal of Pharmaceutics, 555, 228-236. https://doi.org/10.1016/j.ijpharm.2018.11.051

The oral cavity is of great importance to the performance of orally retained formulations, including: orally disintegrating tablets, taste-masked formulations, and buccal/sublingual delivery systems. With regards to in vitro dissolution assessment of... Read More about Application of biorelevant saliva-based dissolution for optimisation of orally disintegrating formulations of felodipine.

Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach (2018)
Journal Article
Lee, J. B., Kim, T. H., Feng, W., Choi, H. G., Zgair, A., Shin, S., …Shin, B. S. (2019). Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach. Pharmaceutical Sciences, 108(2), 1047-1052. https://doi.org/10.1016/j.xphs.2018.09.025

For performance assessment of the lipid-based drug delivery systems (LBDDS), in vitro lipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilisation processes. Much of... Read More about Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach.

Analytical ultracentrifugation in saliva research: Impact of green tea astringency and its significance on the in-vivo aroma release (2018)
Journal Article
Dinu, V., Liu, C., Ali, J., Ayed, C., Gershkovich, P., Adams, G. G., Harding, S. E., & Fisk, I. (2018). Analytical ultracentrifugation in saliva research: Impact of green tea astringency and its significance on the in-vivo aroma release. Scientific Reports, 8, 1-9. https://doi.org/10.1038/s41598-018-31625-w

Current saliva testing methods rely on cutting edge yet expensive techniques for the detection and analysis of genetic material, proteins and biomarkers for clinical use. However, these techniques are limited in scope and often cannot be used with co... Read More about Analytical ultracentrifugation in saliva research: Impact of green tea astringency and its significance on the in-vivo aroma release.

Lipophilic activated ester prodrug approach for drug delivery to the intestinal lymphatic system (2018)
Journal Article
Lee, J. B., Zgair, A., Malec, J., Kim, T. H., Kim, M. G., Ali, J., Qin, C., Feng, W., Chiang, M., Gao, X., Voronin, G., Garces, A., Lau, C. L., Chan, T.-H., Hume, A., McIntosh, T. M., Soukarieh, F., Al-Hayali, M., Cipolla, E., Collins, H. M., …Gershkovich, P. (2018). Lipophilic activated ester prodrug approach for drug delivery to the intestinal lymphatic system. Journal of Controlled Release, 286, 10-19. https://doi.org/10.1016/j.jconrel.2018.07.022

The intestinal lymphatic system plays an important role in the pathophysiology of multiple diseases including lymphomas, cancer metastasis, autoimmune diseases, and human immunodeficiency virus (HIV) infection. It is thus an important compartment for... Read More about Lipophilic activated ester prodrug approach for drug delivery to the intestinal lymphatic system.

Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited (2018)
Journal Article
Constantinescu, C. S., & Gershkovich, P. (2018). Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited. European Journal of Neurology, 25(7), 905-906. https://doi.org/10.1111/ene.13658

Cannabinoids are compounds with pleiotropic properties that act on the cannabinoid receptors, CB1 and CB2, and are divided into endocannabinoids, the endogenous ligands of these receptors, synthetic cannabinoids and phytocannabinoids. The latter are... Read More about Therapeutic cannabinoids in multiple sclerosis: immunomodulation revisited.

Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation (2018)
Journal Article
Citossi, F., Smith, T., Lee, J. B., Segal, J., Gershkovich, P., Stocks, M. J., Bradshaw, T. D., Kellam, B., & Marlow, M. (in press). Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation. Molecular Pharmaceutics, 15(4), https://doi.org/10.1021/acs.molpharmaceut.7b01106

Low molecular weight gelators (LMWGs) of chemotherapeutic drugs represent a valid alternative to the existing poly-mer-based formulations used for targeted delivery of anticancer drugs. Herein we report the design and development of novel self-assemb... Read More about Self-assembling benzothiazole-based gelators: a mechanistic understanding of in vitro bioactivation and gelation.

Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation (2017)
Journal Article
Zgair, A., Lee, J. B., Wong, J. C. M., Taha, D. A., Aram, J., Virgilio, D. D., …Gershkovich, P. (2017). Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation. Scientific Reports, 7, 1-12. https://doi.org/10.1038/s41598-017-15026-z

Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) have well documented immunomodulatory effects in vitro, but not following oral administration in humans. Here we show that oral co-administration of cannabinoids with lipids can substantially increa... Read More about Oral administration of cannabis with lipids leads to high levels of cannabinoids in the intestinal lymphatic system and prominent immunomodulation.

Development of cordycepin formulations for preclinical and clinical studies (2017)
Journal Article
Lee, J. B., Adrower, C., Qin, C., Fischer, P. M., de Moor, C. H., & Gershkovich, P. (2017). Development of cordycepin formulations for preclinical and clinical studies. AAPS PharmSciTech, 18(8), 3219-3226. https://doi.org/10.1208/s12249-017-0795-0

There is extensive literature on in vivo studies with cordycepin but these studies were generally conducted without validation of the various formulations, especially in terms of the solubility of cordycepin in the dosing vehicles used. Cordycepin is... Read More about Development of cordycepin formulations for preclinical and clinical studies.

Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity (2017)
Journal Article
Taha, D. A., Zgair, A., Lee, J. B., de Moor, C. H., Barrett, D. A., Bruce, K. D., …Gershkovich, P. (2017). Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity. European Journal of Pharmaceutical Sciences, 100, 163-175. https://doi.org/10.1016/j.ejps.2017.01.018

The association of lipophilic statins with plasma lipoproteins in the presence of disturbed acid-base balance can modify the pharmacokinetics and tissue distribution of these drugs, resulting in alteration in their efficacy and toxicity profiles. The... Read More about Hyperlipidaemia alone and in combination with acidosis can increase the incidence and severity of statin-induced myotoxicity.

Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays (2017)
Journal Article
Lee, J. B., Zgair, A., Taha, D. A., Zang, X., Kagan, L., Kim, T. H., …Gershkovich, P. (2017). Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays. European Journal of Pharmaceutics and Biopharmaceutics, 114, 38-42. https://doi.org/10.1016/j.ejpb.2016.12.027

In this study, Caco-2 permeability results from different laboratories were compared. Six different sets of apparent permeability coefficient (Papp) values reported in the literature were compared to experimental Papp obtained in our laboratory. The... Read More about Quantitative analysis of lab-to-lab variability in Caco-2 permeability assays.

Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma (2016)
Journal Article
Lee, J. B., Zgair, A., Kim, T. H., Kim, M. G., Yoo, S. D., Fischer, P. M., & Gershkovich, P. (2017). Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma. Journal of Chromatography B, 1040, 73-80. https://doi.org/10.1016/j.jchromb.2016.11.024

Bexarotene is currently marketed for treatment of cutaneous T-cell lymphoma and there has been growing interest in its therapeutic effectiveness for other cancers. Neuroprotective effects of bexarotene have also been reported. In this study, a simple... Read More about Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma.

Linking in vitro lipolysis and microsomal metabolism for the quantitative prediction of oral bioavailability of BCS II drugs administered in lipidic formulations (2016)
Journal Article
Benito-Gallo, P., Marlow, M., Zann, V., Scholes, P., & Gershkovich, P. (in press). Linking in vitro lipolysis and microsomal metabolism for the quantitative prediction of oral bioavailability of BCS II drugs administered in lipidic formulations. Molecular Pharmaceutics, 13(10), https://doi.org/10.1021/acs.molpharmaceut.6b00597

Lipidic formulations (LFs) are increasingly utilized for the delivery of drugs that belong to class II of the Biopharmaceutics Classification System (BCS). The current work proposes, for the first time, the combination of in vitro lipolysis and micro... Read More about Linking in vitro lipolysis and microsomal metabolism for the quantitative prediction of oral bioavailability of BCS II drugs administered in lipidic formulations.

Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines (2016)
Journal Article
Zgair, A., Wong, J. C., Lee, J. B., Mistry, J., Sivak, O., Wasan, K. M., …Gershkovich, P. (2016). Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines. American Journal of Translational Research, 8(8), 3448-3459

There has been an escalating interest in the medicinal use of Cannabis sativa in recent years. Cannabis is often administered orally with fat-containing foods, or in lipid-based pharmaceutical preparations. However, the impact of lipids on the exposu... Read More about Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.

Proposing the use of partial AUC as an adjunctive measure in establishing bioequivalence between deltoid and gluteal administration of long-acting injectable antipsychotics (2016)
Journal Article
Lee, L. H. N., Choi, C., Gershkovich, P., Barr, A. M., Honer, W. G., & Procyshyn, R. M. (2016). Proposing the use of partial AUC as an adjunctive measure in establishing bioequivalence between deltoid and gluteal administration of long-acting injectable antipsychotics. European Journal of Drug Metabolism and Pharmacokinetics, 41(6), 659-664. https://doi.org/10.1007/s13318-016-0348-z

The maximum plasma concentration (Cmax) and the area under the plasma concentration–time curve (AUC) are commonly used to establish bioequivalence between two formulations of the same oral medication. Similarly, these pharmacokinetic parameters have... Read More about Proposing the use of partial AUC as an adjunctive measure in establishing bioequivalence between deltoid and gluteal administration of long-acting injectable antipsychotics.

The role of acid-base imbalance in statin-induced myotoxicity (2016)
Journal Article
Taha, D. A., de Moor, C. H., Barrett, D. A., Lee, J. B., Gandhi, R. D., Hoo, C. W., & Gershkovich, P. (2016). The role of acid-base imbalance in statin-induced myotoxicity. Translational Research, The Journal of Laboratory and Clinical Medicine, 174, 140-160.e14. https://doi.org/10.1016/j.trsl.2016.03.015

Disturbances in acid-base balance, such as acidosis and alkalosis, have potential to alter the pharmacological and toxicological outcomes of statin therapy. Statins are commonly prescribed for elderly patients who have multiple co-morbidities such as... Read More about The role of acid-base imbalance in statin-induced myotoxicity.

In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B (2015)
Journal Article
Qazzaz, M. E., Raja, V. J., Lim, K.-H., Kam, T.-S., Lee, J. B., Gershkovich, P., & Bradshaw, T. D. (2016). In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B. Cancer Letters, 370(2), https://doi.org/10.1016/j.canlet.2015.10.013

Natural products play a pivotal role in medicine especially in the cancer arena. Many drugs that are currently used in cancer chemotherapy originated from or were inspired by nature. Jerantinine B (JB) is one of seven novel Aspidosperma indole alkalo... Read More about In vitro anticancer properties and biological evaluation of novel natural alkaloid jerantinine B.

Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis (2015)
Journal Article
Benito-Gallo, P., Franceschetto, A., Wong, J. C., Marlow, M., Zann, V., Scholes, P., & Gershkovich, P. (2015). Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis. European Journal of Pharmaceutics and Biopharmaceutics, 93, https://doi.org/10.1016/j.ejpb.2015.04.027

Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of po... Read More about Chain length affects pancreatic lipase activity and the extent and pH–time profile of triglyceride lipolysis.

Characterisation of human saliva as a platform for oral dissolution medium development (2015)
Journal Article
Gittings, S., Turnbull, N., Henry, B., Roberts, C. J., & Gershkovich, P. (2015). Characterisation of human saliva as a platform for oral dissolution medium development. European Journal of Pharmaceutics and Biopharmaceutics, 91, 16-24. https://doi.org/10.1016/j.ejpb.2015.01.007

Human saliva is a biological fluid of great importance in the field of dissolution testing. However, until now, no consensus has been reached on its key characteristics relevant to dissolution testing. As a result, it is difficult to select or develo... Read More about Characterisation of human saliva as a platform for oral dissolution medium development.